Methamphetamine (MA) use disorder is a major problem for over 3 million people world-wide, with no FDA- approved pharmacotherapy. However, anti-addiction drug vaccines hold promise by inducing drug specific antibodies that form antibody-MA complexes in the blood, which are too large to cross the blood-brain barrier, thus reducing the rate and quantity of MA's brain entry. This inhibits MA's psychoactive effects. This study will evaluate the safety and dosing of a MA vaccine - KOsten-MethAmphetamine (KO-MA) vaccine - to produce anti-MA antibodies (AB) in MA dependent human subjects. KO-MA links MA to a tetanus toxoid (TT) carrier through succinyl methamphetamine (SMA) , and the TT-SMA conjugate is formulated with a potent adjuvant system SA-702, consisting of alum and the co-adjuvant, entolimod (recombinant TRL-5 receptor agonist). The KO-MA vaccine is superior to our previous TA-CD cocaine vaccine because it generates substantially higher levels of anti-drug AB in animals. Previous cocaine and nicotine vaccine clinical trials failed because many patients did not produce sufficient antibody responses for efficacy and FDA approval. These higher AB levels with KO-MA reflect to a combination of a more potent carrier protein (tetanus toxoid- TT vs cholera toxoid subunit B for TA-CD) and an additional potent adjuvant system SA-702. Our strong preliminary data with KO-SA demonstrates substantially high anti-MA AB levels capable of reducing MA induced behavioral effects in rodents. KO-MA also shows no potentiation of MA cardiovascular effects and no pyrogenecity or any other significant toxicity in animal studies. The KO-MA is stable for 12 months by physiochemical assays. Our two goals are: (1) manufacture KO-MA and do accelerated stability testing for 3 months at 25C and (2) conduct human studies in normal controls and MA users. The first human study (STTR- Phase 1) tests the safety and efficacy of proposed doses of entolimod in normal humans by comparing a single dose of TT +SA-702 to TT + alum. We expect that TT +SA-702 should double the anti-TT AB level of TT +alum. The second study (STTR-Phase 2=FDA Phase 1) will compare medical safety and efficacy of cGMP manufactured KO-MA at 2 doses (8 g and 32 g) to placebo. These two doses are administered three times over 6 weeks in two separate cohorts of 24 MA users/cohort. We expect KO-MA to produce substantial levels of anti-MA AB (above 50 g/ml) with no significant adverse effects. Entolimod has been given to almost 200 humans at 30 times the proposed dose. Thus, humans have already safely gotten all the major components of KO-MA: TT, Alum (FDA approved) and entolimod adjuvant. We have had two pre-IND communications with FDA, including a review of our human study protocol, and have responded to all the FDA concerns by conducting the studies requested by them for filing a successful IND, except the studies proposed here. If approved, this KO- MA vaccine would be the first FDA- approved therapy for MA abuse.